Haematologica 2003 - Supplements

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Thalidomide as Rescue of Relapses after
Haematopoietic Transplantation in Multiple Myeloma:
Results of a Spanish Multicentre Ragistry Including 70
patients
A Alegre1, JJ Gil-Fernández2, J. Bladé, 3, C. Martínez-
Chamorro2, L. Rosiñol3, A Sureda4, A. Escudero2, P.
Font5, A. Alonso5,P. Sánchez-Godoy6, C. Burgaleta7
L.F.Casado8, A. Granda1, B.Aguado1, E. Prieto8, JM
Fernández-Rañada1
Hospital Universitario de la Princesa(Madrid)1, Clínica
Ruber(Madrid)2, Hospital Clínic (Barcelona)3, Hospital Santa Creu
i Sant Pau (Barcelona)4 Clínica Moncloa (Madrid)5, Hospital
Severo Ochoa- Leganés (Madrid)6, Hospital Alcalá de Henares
(Madrid) 7 , Hospital Virgen de la Salud (Toledo) 8and Fundación
Jiménez Díaz (Madrid) 9 SPAIN. Grupo Español de Mieloma-GEM
(GETH, PETHEMA and GELTAMO)
Introduction.Thalidomide and its analogues have emerged as a
new class of active agents in multiple myeloma with a response
rate ranging from 30% to 40% in refractory patients and from
70% to 90% when associated to dexamethasone in symptomatic
de novo patients. We present the experience of a spanish
multicentre registry using this drug in MM patients as rescue for
relapse after hematopoietic transplantation.
Patients and treatment.Since November 1999 seventy patients
with MM have received oral Thalidomide as rescue for relapse
after autologous (65) or allogeneic (5) hematopoietic
transplantation The treatment included oral Thalimodide® 100
mg (Grunnenthal, Germany): 200 mg/d, escalating doses every
14 d, according tolerance until a maximum dayly dose of 800 mg.
Median dose received was 400 mg/d. In 25 patients thalidomide
were used alone. Rest of the patients received this drug associated
to Dexamethasone ( 20-40 mg x 4 every 21-28 d. Six patients
received also low dose oral cyclophosphamide 150 mg x w. In
seven cases thalidomide were used associated to
polichemotherapy following the DECP 24 h i.v. infusional
scheme ( dexamethasona, etoposide, cyclophosphamide, and
platinum). Patients with bone lesions also received
bisphosphonates iv monthly.
Results. 61 patients were evaluable for response*: 29 patients
achieved favourable response (47%) See Table. Median treatment
duration was 5 months (0.5-36). Only 1 patient, of 7 known
cases with del cr13, showed favourable response. However, 7 out
of 15 patients with multiple plasmocitomas showed objective
response. Main toxicity > = grade I according WHO, was:
constipation (50%), somnolence (33%) and peripheral
neuropathy (12%). 2 cases presented venous thromboembolis;
one with APCR coagulative test positive; and 4 patient showed
cardiotoxicity. One case of TRM probably for cardiac failure
was observed. Treatment was interrupted due to toxicity in 6
cases (10%). After a median follow up of 14 months (2-30) the
OS and EFS estimated at 2 years was 50% and 20% respectively.
Table of Results
Response(Reduction of M Component) N Patients (%)
Complete Response 2(2%)
Objective response (>50%) 12 (20%)
Minimal Repsonse (25%-50%) 15 (25%)
Total favourable response 29(47%)
Non response-Stable disease 9(15%)
Progression 23 (38%)
Median duration of Response (months) 7(2-26)
*Patients evaluables: (at least 6 weeks on treatment)
Comments and Conclussions. Oral thalidomide alone or
combined with steroids or chemotherapy induces a considerable
response rate in this population of MM with poor prognostic.
Definitively, this drug should be considered between the
therapeutic options for rescue of MM relapsing after transplant.
Its optimal effects are observed when associated to
dexamethasone. The stable and long duration response, observed
in some patients at low dose for long term treatment, suggests a
possible role of this drug as maintenance treatment that need to
be explored. In our series , patients with del cr13 showed poor
response but some cases with multiple plasmocytomas responded.
The toxicity presented with this drug make necessary the
introduction of new thalidomide analogs with similar effects but
without that toxicity (Inmunomodulatory drugs: IMID as
Revimid®, CC5013). The exact dose, timing and treatment
duration of these agents and its more efficacious combinations
need to be explored in randomized controlled trials.Also is
necessary to evaluate its potential role in smoldering MM to
prevent or retard evolution to open MM; in symptomatic de novo
patients instead of standard induction regimen and also as
maintenance treatment modulating minimal residual disease.
313
Thalidomide in relapsed and refractory multiple
myeloma.: a retrospective analysis of efficacity and
toxicity
L. Schauvliege, A. Janssens, A. Vantilborgh, F. Offner, L.
Noens.
Department of Hematology, Ghent University Hospital, Ghent.
Thalidomide and its analogues have emerged as a novel class of
therapeutics in multiple myeloma.The aim of this retrospective
analysis was to evaluate the activity and toxicity of thalidomide
in relapsed and refractory myeloma patients at the University
hospital of Ghent. From april 2000 to november 2002, 40 patients
(16males/24females) with relapsed/refractory myeloma have
been treated with thalidomide. Before starting thalidomide
different schemes of chemotherapy - like VAD, VCMP,
interferon-, melfalan or cyclofosfamide- often combined with
radiotherapy were applied. Sixteen patients were relapsing after
an autologous stem cell transplant.
Results: The mean age was 62 years ( range 39 to 83 y). The
myeloma subtypes were distributed as follows: IgG (n=25), IgA
(n=8), light chain (n=6), non secreting (n=1).
The maximum tolerated dose of thalidomide varied between 150
mg to 400mg, with an average dose of 250 mg. The duration of
treatment varied from 23 to 861 days.
On an intent-to-treat basis, the 40 patients were evaluable for
response after 6 weeks of therapy. Overall response was 37.5%
(n=15/40). Four patients showed ≥50% reduction in serum or
urinary M-protein concentration, eleven patients showed≥25%
tumor reduction. Nine patients had stable disease.
On an intent-to-treat basis, overall response after 3 months of
therapy was also 37.5% (n=15/40). Seven patients had ≥50%
reduction in serum or urinary M-protein concentration, eight
patients reached≥25% tumor reduction, four patients could be
considered having stable disease.
Therapy had to be stopped in thirteen patients because of severe
side effects. Nervous system adverse events were seen most
frequently (paresthesia (n=3), dyskinesia (n=2), vertigo (n=2)),
followed by digestive problems (constipation (n=2), nausea
(n=1)) and infectious complications (n=3). The duration of
therapy in this subgroup ranged from 23 to 543 days.
The treatment was also stopped in eleven patients due to
progressive disease.
Conclusion: We can confirm the efficacity of thalidomide in
relapsed and refractory MM with an overall response rate of
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